The identification of the entire genome sequences of many species, including humans, has set the stage for rapid advancements in the field of functional genomics. Information generated from functional analysis of genes will, in the long run, have major benefits for the prevention, diagnosis and management of many diseases which have been difficult to control. Given the large volume of data from the genome of complex organisms, functional genetic studies demand high-throughput methods to rapidly elucidate the function of many genes in parallel. Cell-based microarray systems are simple and low-cost, yet powerful tools that allow large-scale manipulation of genes in cells and analysis of corresponding downstream phenotypes. Currently, these arrays are realized by using either microwell plates that spatially segregate reagents using physical walls or solid substrates (glass or polystyrene) “printed” in certain spots with reagents suspended in a gel material. The printing method, also known as reverse transfection, offers higher density and simplified fluid handling once the reagents are printed and several groups have shown its potential for high-throughput studies of gene function. Nevertheless, this technique is inflexible in timing of delivery and removal of reagents, which limits the possibility of exposure of cells to a biochemical for a desired time period, and addition of certain components is required to stabilize transfection reagents. Most importantly, the printed gel that immobilizes reagents on the surface, by necessity, becomes the substrate to which cells attach and grow. This is a major concern for phenotypic assays since the influence of interactions between cells and their ECM on gene expression patterns of cells is ignored.
New methods are needed for cellular arrays to allow for parallel analysis of multiple genes in one assay.